Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484056 | SCV000570578 | likely pathogenic | not provided | 2018-03-20 | criteria provided, single submitter | clinical testing | The Y433X variant in the EXOC6B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y433X variant was not observed in approximately 5900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Y433X variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
Geisinger Autism and Developmental Medicine Institute, |
RCV000484056 | SCV000804396 | likely pathogenic | not provided | 2018-01-23 | criteria provided, single submitter | provider interpretation | This 7 year old male with a history of seizures, severe intellectual disability, microcephaly, osteopenia, and short stature is heterozygous for a maternally-inherited nonsense variant in EXOC6B. He also has eczema that is explained by a FLG pathogenic variant and hypospadias that was repaired as an infant. He initially presented with complex febrile seizures between 2-3 years of age that progressed to global tonicity with flexion and extension, mouth clicking, and perioral cyanosis. A brain MRI at 1 year of age showed symmetrical volume loss involving the bilateral peri-arterial white matter with compensatory enlargement and mild scalloping of both atria of the lateral ventricles compatible with periventricular leukomalacia. Asymmetrical low-lying right cerebellar tonsil was also noted. Patient's mother has not undergone an MRI or renal studies, and reportedly has scoliosis but no developmental or neurological concerns. This variant is absent from gnomAD and loss of normal protein function is predicted either through protein truncation or nonsense-mediated mRNA decay. This individual also has a heterozygous paternally-inherited missense variant of uncertain significance in AUTS2. The patient's father reportedly has no overlapping phenotype. |